Abstract / Summary
Abstract Background: Pancreatic surveillance commonly detects pancreatic cysts, most of which are presumed intraductal papillary mucinous neoplasms (IPMN). FUT2, the gene responsible for secretor status, has been implicated in IPMN development, although not with pancreatic cancer risk. Methods: We evaluated the association between inactivating variants in FUT2, FUT3 and ABO and pancreatic cysts in 1,865 patients in the multicenter Cancer of the Pancreas Screening (CAPS) cohort. Multivariable logistic regression was performed to estimate adjusted odds for presumed IPMN prevalence. A Johns Hopkins surgical cohort of 1582 patients with IPMN, pancreatic ductal adenocarcinoma (PDAC), or carcinoma arising from IPMN was analyzed to examine trend in variant proportion by malignant progression. Results: In the CAPS cohort, older age (OR per year; 1.06 [1.05-1.07]; p < 0.001), FUT2-null (non-secretors) (OR: 1.66 [1.30-2.12]; p<0.001), non-O blood group (OR: 1.31 [1.06-1.62]; p=0.012), having familial-only vs. genetic/familial risk (OR: 1.49 [1.20-1.85] p<0.001), and participating site (OR; 2.20 [1.78-2.73], p<0.001) were associated with having pancreatic cysts. There were no significant FUT2/ABO presumed IPMN prevalence interactions. In the combined cohort, the proportion of FUT2-null patients with IPMN without carcinoma (by imaging or pathology) was 319 (27.4%) of 1162; 57 (24.3% of 234) with IPMN and carcinoma, and 225 (22.5%) of 998 with PDAC alone (p=0.009 for trend). Conclusions: IPMN is more prevalent in FUT2-null patients under pancreas surveillance, but the increased FUT2-null prevalence is not observed in patients with IPMN with carcinoma. Impact: Pancreatic cancer risk conferred by having IPMN may be lower in FUT2-null compared to FUT2-intact individuals.